Synthesis of α-oxycarbanilinophosphonates and their anticholinesterase activities: the most potent derivative is bound to the peripheral site of acetylcholinesterase. (June 2013)

• Record Type: Journal Article
• Authors: Kaboudin, Babak; Emadi, Saeed; Faghihi, Mohammad Reza; Fallahi, Maryam; Sheikh-Hasani, Vahid
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 28:Number 3(2013:Jun.)
• Page Start: 576
• Page End: 582
• Publication Date: 2013-06
• Subjects: Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.3109/14756366.2012.663362
• Languages: English
• ISSNs: 1475-6366

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p>A novel method has been developed for the synthesis of α-oxycarbanilino phosphonates through a reaction of α-hydroxyphosphonates with isocyanate under microwave irradiation. The synthesized compounds were evaluated for their acetylcholinesterase (AChE) inhibition potency through IC₅₀determination. Molecular modelling studies suggest that the most potent inhibitor (compound <bold>4h</bold>, IC₅₀ = 6.36 µM) is bound to the peripheral site of AChE, which suggests that it decreases the catalytic activity not through binding to the active site but through blocking the entrance of the active site gorge. This puts forward the potential of compound <bold>4h</bold> and its derivatives to be used in the design of dual inhibitors: inhibition of the catalytic activity of AChE and of amyloid β aggregation.</p> </abstract>